The nature of the IgA deposits in renal tissue and the mechanism of renal injury in IgA nephropathy, Schonlein-Henoch purpura, and liver cirrhosis-associated glomerulonephritis are not clear. Although the etiology of these diseases remains unknown, clinical evidence supports the concept of an immune complex disease. An experimental model for IgA-associated glomerulonephritis has not been developed because serum concentration of IgA is relatively low and it is very difficult to obtain sufficient IgA to a specific antigen. An alternative approach to the elucidation of the problem is through the use of antigen-binding-IgA-myeloma. The objective of the present proposal is to investigate the pathogenetic mechanism through which soluble IgA immune complexes induce renal injury in experimental animals using covalently cross-linked immune complexes. Model IgA complexes' behavior in vivo will be determined by studying their clearance kinetics from circulation and their mode of interaction with the reticuloendothelial system, with special reference to their fate in the liver. The effects of the molecular form of IgA, the complex lattice composition and size on glomerular deposition and persistence will be evaluated quantitatively. The potential of defined soluble IgA complexes to induce renal injury and the resulting course of nephritis will be assessed by morphological andd immunohistological changes in glomeruli of experimental animals. The role of complement as a mediator of the inflammatory process in IgA nephropathy will be tested in normal and decomplemented animals. Influence of concomitant deposition of other classes of immunoglobulins on renal injury will be examined. A sensitive method for specific detection and characterization of circulating IgA immune complexes will also be developed. The establishement of a laboratory model for the study of the pathogenesis of IgA-associated glomerulonephritis will provide an understanding of the processes involved in human diseases.